PROJECT SUMMARY This proposal details a five-year mentored training program for the career development and advancement of Dr. Jose A. Gomez, into an independent investigator. Dr. Gomez is a Research Instructor in the Division of Clinical Pharmacology at Vanderbilt University. He graduated with a Doctorate in Pharmacology from Case Western Reserve University. In 2009, he joined Dr. Victor J. Dzau's laboratory as a Post-Doctoral Fellow at Duke University, and became interested in blood pressure control and hypertension. He joined Vanderbilt University as Research Instructor in the Department of Medicine/Division of Clinical Pharmacology in 2015. During his K01 award, he will work with Dr. Harrison in close collaboration with Dr. Pozzi and Dr. Harris. As a postdoctoral fellow he defined the role of renal mesenchymal stromal cells in blood pressure homeostasis. He found that adult kidney stem/progenitor cells have the capacity to differentiate into JG-like cells and/or contribute to JG cell expansion. In a second project he contributed to a study that found that renal MSCs are recruited via the Cox2-PGE2-EP4 pathway. He aslo investigated the mechanisms by which adult stem cells differentiate into specialized tissues, and determined that Sfrp2 plays an essential role in cardiac regeneration by promoting the differentiation of c-Kit+ cardiac progenitor cells to cardiomyocytes. Now as a Clinical Instructor in Vanderbilt University, under the mentorship of Dr. David Harrison, he is elucidating the transcriptional regulators that play a role in the programming of renal progenitor cells into Juxtaglomerular cells. He found that Sox6 is expressed in renin producing cells in the developing kidney and in the adult kidney after stimulation that promotes JG cell expansion. This suggests a novel role for Sox6 in renin cell fate specification and thereby in renal development and physiology. His preliminary data shows that Sox6 is required in the conversion of renal MSCs to renin expressing cells in vitro. In this K01 proposal, he will characterize a new key function of Sox6 in blood pressure homeostasis and Juxtaglomerular cell fate. The studies proposed in this K01, aim at identifying the mechanisms by which Sox6 plays a role in blood pressure homeostasis, and will open new opportunities for the therapy of hypertension. During his planned research, Dr. Gomez will become experienced in in vitro and in vivo approaches to study hypertension. In addition, his training plan includes didactic courses, seminars, and participation in career development programs at Vanderbilt that promote the retention and tenure of junior faculty members. Dr. Harrison and Dr. Gomez have developed a timeline for his career development and training activities that will enable him to compete for funding and to develop into an independent investigator in the field hypertension. 100% of his time will be protected for activities directly related to his career development. Vanderbilt University's research and academic environment is highly exceptional for trainee career development.